Hydrochloric Acid → 2,3-Difluoro-5-(2-hydroxyethyl)benzaldehyde

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Reaction Conditions

Reaction Steps

2,2,6,6-Tetramethylpiperidine (6.15 mL) was added to a solution of n-butyllithium in hexanes (1.6M, 22.8 mL) at −70° C. A solution of 2-(3,4-difluorophenyl)ethanol (example 32, step a) (1.92 g) in THF (25 mL) was added dropwise. THF (25 mL) was added and the mixture stirred at −70° C. for 6 h. DMF (4.7 mL) was then added and the mixture stirred for 1 h at −70° C. The mixture was then allowed to warm to RT and stirred for 70 h. Aqueous HCl solution (2M, 10 mL) was added followed by ethyl acetate (20 mL) and the layers separated. The aqueous phase was extracted with ethyl acetate (2×20 mL). The combined organic solutions were washed with brine (20 mL), dried over magnesium sulphate, filtered and evaporated in vacuo. Purification was by silica gel chromatography eluting with 4:1 to 2:1 isohexane:diethyl ether gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a yellow oil. Yield 1.9 g.

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